Analysis of risk factors for recurrence in infertile endometrial cancer patients after in vitro fertilization treatment

PurposeTo investigate the oncologic outcomes of patients with early-stage endometrioid endometrial cancer (EEC) treated with in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) following fertility-sparing treatment (FST).MethodsA total of 62 patients who underwent IVF/ICSI treatment in a single fertility center between June 2010 and December 2021 after conservative treatment for early-stage EEC were assigned to a recurrence group and a non-recurrence group. Their clinical characteristics and disease outcomes were retrospectively evaluated.ResultsThe 62 women with complete remission (CR) after FST for EEC underwent 103 IVF cycles, resulting in 41 fresh embryo transfers (ETs) and 70 frozen–thawed transfers; 27 (43.55%) achieved clinical pregnancies, and 20 (32.26%) gave birth to a total of 23 live neonates. Additionally, nine patients had live births from natural pregnancies after IVF failure, bringing the cumulative live birth rate to 46.77% (29/62). After a median follow-up period of 53.88 months (range 20.2–127.5 months), 17 patients (27.42%) experienced recurrence within 2.8 to 57.9 months after the first controlled ovarian stimulation (COS). The probability of relapse at 1, 2, and 3 years after the initiation of COS was 14.52% (9/62), 21% (13/62), and 25.81% (16/62), respectively. Factors such as the time to CR, the time to IVF, the frequency of COS, maintenance treatment before IVF, and histology type were not found to significantly affect recurrence (p = 0.079, 0.182, 0.093, 0.267, and 0.41, respectively). Live births (hazard ratio (HR): 0.28, 95% CI: 0.082–0.962, p = 0.043) and the protocol of letrozole plus gonadotropin-releasing hormone (GnRH) antagonist/agonist used during IVF (HR: 0.1, 95% CI: 0.011–0.882, p = 0.038) were identified as independent favorable factors for recurrence.ConclusionsLive birth was associated with decreased recurrence of EEC. Reducing estrogen levels during COS may serve to mitigate the risk of endometrial cancer recurrence

Robust joint analysis allowing for model uncertainty in two-stage genetic association studies

<p>Abstract</p> <p>Background</p> <p>The cost efficient two-stage design is often used in genome-wide association studies (GWASs) in searching for genetic loci underlying the susceptibility for complex diseases. Replication-based analysis, which considers data from each stage separately, often suffers from loss of efficiency. Joint test that combines data from both stages has been proposed and widely used to improve efficiency. However, existing joint analyses are based on test statistics derived under an assumed genetic model, and thus might not have robust performance when the assumed genetic model is not appropriate.</p> <p>Results</p> <p>In this paper, we propose joint analyses based on two robust tests, MERT and MAX3, for GWASs under a two-stage design. We developed computationally efficient procedures and formulas for significant level evaluation and power calculation. The performances of the proposed approaches are investigated through the extensive simulation studies and a real example. Numerical results show that the joint analysis based on the MAX3 test statistic has the best overall performance.</p> <p>Conclusions</p> <p>MAX3 joint analysis is the most robust procedure among the considered joint analyses, and we recommend using it in a two-stage genome-wide association study.</p

Reproductive Outcomes of In Vitro Fertilization and Fresh Embryo Transfer in Infertile Women With Adenomyosis: A Retrospective Cohort Study

BackgroundAdenomyosis is commonly encountered in infertile women; however, it is still unclear whether adenomyosis has a detrimental effect on in vitro fertilization and embryo transfer (IVF-ET) outcomes.MethodWe enrolled 1146 patients with adenomyosis and 1146 frequency-matched control women in a 1:1 ratio based on age, BMI, and basal follicle-stimulating hormone (FSH) level. After controlling for other factors, the rates of clinical pregnancy, miscarriage, live birth, and obstetric complications were compared between two groups.ResultsThere was no significant difference in clinical pregnancy rate between the two groups (38.1% vs. 41.6%; P=0.088). The implantation rate (25.6% versus 28.6%, P=0.027) and live birth rate (26% versus 31.5%, P=0.004) were significantly lower in the women with adenomyosis than in the controls. The miscarriage rate in the adenomyosis group was higher than that in the control group (29.1% versus 17.2%, P=0.001). After adjusting for confounding factors, multivariate analysis showed the clinical pregnancy rate was not statistically different between the two groups (OR: 0.852, P=0.070). In the adenomyosis group, the rate of miscarriage(OR: 1.877, P=0.000), placenta previa (OR: 2.996, P=0.042)and preeclampsia (OR: 2.287, P=0.042)were increased significantly, while live birth rate (OR: 0.541, P=0.000) was reduced significantly than control group.ConclusionAdenomyosis has negative effect on IVF-ET outcomes in which miscarriage risk increased, live birth rate reduced and obstetric complications increased

FAN: Fatigue-Aware Network for Click-Through Rate Prediction in E-commerce Recommendation

Since clicks usually contain heavy noise, increasing research efforts have been devoted to modeling implicit negative user behaviors (i.e., non-clicks). However, they either rely on explicit negative user behaviors (e.g., dislikes) or simply treat non-clicks as negative feedback, failing to learn negative user interests comprehensively. In such situations, users may experience fatigue because of seeing too many similar recommendations. In this paper, we propose Fatigue-Aware Network (FAN), a novel CTR model that directly perceives user fatigue from non-clicks. Specifically, we first apply Fourier Transformation to the time series generated from non-clicks, obtaining its frequency spectrum which contains comprehensive information about user fatigue. Then the frequency spectrum is modulated by category information of the target item to model the bias that both the upper bound of fatigue and users' patience is different for different categories. Moreover, a gating network is adopted to model the confidence of user fatigue and an auxiliary task is designed to guide the learning of user fatigue, so we can obtain a well-learned fatigue representation and combine it with user interests for the final CTR prediction. Experimental results on real-world datasets validate the superiority of FAN and online A/B tests also show FAN outperforms representative CTR models significantly

Structural and Lipidomic Alterations of Striatal Myelin in 16p11.2 Deletion Mouse Model of Autism Spectrum Disorder

Myelin abnormalities have been observed in autism spectrum disorder (ASD). In this study, we seek to discover myelin-related changes in the striatum, a key brain region responsible for core ASD features, using the 16p11.2 deletion (16p11.2±) mouse model of ASD. We found downregulated expression of multiple myelin genes and decreased myelin thickness in the striatum of 16p11.2± mice versus wild type controls. Moreover, given that myelin is the main reservoir of brain lipids and that increasing evidence has linked dysregulation of lipid metabolism to ASD, we performed lipidomic analysis and discovered decreased levels of certain species of sphingomyelin, hexosyl ceramide and their common precursor, ceramide, in 16p11.2± striatum, all of which are major myelin components. We further identified lack of ceramide synthase 2 as the possible reason behind the decrease in these lipid species. Taken together, our data suggest a role for myelin and myelin lipids in ASD development

MindShift: Leveraging Large Language Models for Mental-States-Based Problematic Smartphone Use Intervention

Problematic smartphone use negatively affects physical and mental health. Despite the wide range of prior research, existing persuasive techniques are not flexible enough to provide dynamic persuasion content based on users' physical contexts and mental states. We first conduct a Wizard-of-Oz study (N=12) and an interview study (N=10) to summarize the mental states behind problematic smartphone use: boredom, stress, and inertia. This informs our design of four persuasion strategies: understanding, comforting, evoking, and scaffolding habits. We leverage large language models (LLMs) to enable the automatic and dynamic generation of effective persuasion content. We develop MindShift, a novel LLM-powered problematic smartphone use intervention technique. MindShift takes users' in-the-moment physical contexts, mental states, app usage behaviors, users' goals & habits as input, and generates high-quality and flexible persuasive content with appropriate persuasion strategies. We conduct a 5-week field experiment (N=25) to compare MindShift with baseline techniques. The results show that MindShift significantly improves intervention acceptance rates by 17.8-22.5% and reduces smartphone use frequency by 12.1-14.4%. Moreover, users have a significant drop in smartphone addiction scale scores and a rise in self-efficacy. Our study sheds light on the potential of leveraging LLMs for context-aware persuasion in other behavior change domains

Paternal genetic affinity between western Austronesians and Daic populations

<p>Abstract</p> <p>Background</p> <p>Austronesian is a linguistic family spread in most areas of the Southeast Asia, the Pacific Ocean, and the Indian Ocean. Based on their linguistic similarity, this linguistic family included Malayo-Polynesians and Taiwan aborigines. The linguistic similarity also led to the controversial hypothesis that Taiwan is the homeland of all the Malayo-Polynesians, a hypothesis that has been debated by ethnologists, linguists, archaeologists, and geneticists. It is well accepted that the Eastern Austronesians (Micronesians and Polynesians) derived from the Western Austronesians (Island Southeast Asians and Taiwanese), and that the Daic populations on the mainland are supposed to be the headstream of all the Austronesian populations.</p> <p>Results</p> <p>In this report, we studied 20 SNPs and 7 STRs in the non-recombining region of the 1,509 Y chromosomes from 30 China Daic populations, 23 Indonesian and Vietnam Malayo-Polynesian populations, and 11 Taiwan aboriginal populations. These three groups show many resemblances in paternal lineages. Admixture analyses demonstrated that the Daic populations are hardly influenced by Han Chinese genetically, and that they make up the largest proportion of Indonesians. Most of the population samples contain a high frequency of haplogroup O1a-M119, which is nearly absent in other ethnic families. The STR network of haplogroup O1a* illustrated that Indonesian lineages did not derive from Taiwan aborigines as linguistic studies suggest, but from Daic populations.</p> <p>Conclusion</p> <p>We show that, in contrast to the Taiwan homeland hypothesis, the Island Southeast Asians do not have a Taiwan origin based on their paternal lineages. Furthermore, we show that both Taiwan aborigines and Indonesians likely derived from the Daic populations based on their paternal lineages. These two populations seem to have evolved independently of each other. Our results indicate that a super-phylum, which includes Taiwan aborigines, Daic, and Malayo-Polynesians, is genetically educible.</p

An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance

Colorectal cancer (CRC) patients develop recurrence after chemotherapy owing to the survival of stem cell-like cells referred to as cancer stem-like cells (CSCs). The origin of CSCs is linked to the epithelial–mesenchymal transition (EMT) process. Currently, it remains poorly understood how EMT programmes enable CSCs residing in the tumour microenvironment to escape the effects of chemotherapy. This study identifies a key molecular pathway that is responsible for the formation of drug-resistant CSC populations. Using a modified yeast-2-hybrid system and 2D gel-based proteomics methods, we show that the E3-ubiquitin ligase FBXW7 directly binds and degrades the EMT-inducing transcription factor ZEB2 in a phosphorylation-dependent manner. Loss of FBXW7 induces an EMT that can be effectively reversed by knockdown of ZEB2. The FBXW7-ZEB2 axis regulates such important cancer cell features, as stemness/dedifferentiation, chemoresistance and cell migration in vitro, ex vivo and in animal models of metastasis. High expression of ZEB2 in cancer tissues defines the reduced ZEB2 expression in the cancer-associated stroma in patients and in murine intestinal organoids, demonstrating a tumour-stromal crosstalk that modulates a niche and EMT activation. Our study thus uncovers a new molecular mechanism, by which the CRC cells display differences in resistance to chemotherapy and metastatic potential

Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells

Calycosin, one of small molecules derived from astragalus, has anti-tumor effects in various tumors. However, the effects of calycosin on papillary thyroid cancer (PTC) remain unclear. This study aimed to explore the anti-tumor ability of calycosin on human PTC and its potential mechanisms. The B-CPAP cells were treated with calycosin, then cell proliferation, apoptosis and invasiveness were measured by CCK8 assay, flow cytometry, wound healing and transwell invasion assay, respectively. The cells were also performed by whole transcriptome microarray bioinformatics analysis. Apoptosis and autophagy-related markers or proteins were measured by qRT-PCR or western blot. Sestrin2-mediated AMPK/mTOR pathways were determined by western blot. We found that calycosin inhibited migration and invasion of B-CPAP cells and induced apoptosis (Bax/Bcl-2) and autophagy (LC3II/I, Beclin1) of B-CPAP cells. Differential expressed genes were screened between the calycosin-treated cells and control (524 genes upregulated and 328 genes downregulated). The pathway enrichment suggested that the role of calycosin in B-CPAP cells is closely related to apoptosis-related genes and p70S6 Kinase. Transmission electron microscopy found an increase in autophagosomes in calycosin-treated cells. Sestrin2 in human PTC tissues and B-CPAP cells was lower than in normal thyroid tissues and cells. And the pharmacological effects of calycosin in PTC cells were related to Sestrin2 activation, increased p-AMPK and inhibited p-mTOR and p-p70S6Kinase; these alterations were reversed when silencing Sestrin2. In conclusion, calycosin has an inhibitory effect on PTC via promoting apoptosis and autophagy through the Sestrin2/AMPK/mTOR pathway

RESEARCH ON VIBRATION CHARACTERISTICS OF THE THICK DISC LADDER

Ladder type disc acoustic radiator is widely used in high power ultrasonic field. The frequency equation of stepped thickness disk in free boundary condition are derived based on Mindlin theory from the acoustic point of application and The frequency equation was numerically solved,At the same time,the effects of geometric parameters on the frequency is analyzed. The results show that when the other parameters are constant,the frequency increases with the increase of the disk and the base ring thickness,and decreases with the diameter increases,increases with the increasing diameter. The test results of the calculated frequencies and finite element simulation and experiment is consistent with the basic. Design of bending vibration radiator the conclusion of the thick disc provides the theory reference and the frequency of debugging basis